We have found evidence that histamine stimulated pancreatic secretion and potentiates the effect of other pancreatid stimulants. The nature of this control and its interrelationship with other controlling parameters remains to be explored. The physiological relationship of histamine to known pancreatic stimulants (i.e., CCK-Pz, acetylcholine, chymodenin) must be determined. We will utilize H2 blockers toward this end. Such investigation will not only help define the control of pancreatic secretion, but may also provide insight into the general types of interactions among hormonal and local agents controlling exocrine secretion. We plan to primarily use the isolated in vitro rabbit pancreas preparation developed by Rothman. This is superfusion independent of vascular supply and therefore offers an ideal controlled system to study the direct effect of histamine on the pancreatic secretory cells and to study the interrelationship between controlling agents. The observation that histamine stimulates enzyme secretion from the pancreas and H2 blockers inhibit both histaminic and hormonal stimulation suggests the use of histamine as a palliative agent for the treatment of pancreatitis. We plan to investigate whether cimetidine, an H2 blocker, reduces the signs and symptoms of pancreatitis. These results, in conjunction with the animal studies might reveal something of the etiology of pancreatitis as well as provide a control.